There are a couple of interesting points from this year’s ASCO. I thought one of the datasets that people will certainly pay attention to is the extended follow-up of the frontline pembrolizumab axitinib dataset, the KEYNOTE 426 clinical trial. The two observations that I thought were interesting and caught my attention – the overall survival of the good risk subset, the hazard ratio in the first publication in The New England Journal of Medicine was positive in favour of the doublet versus Sutent by landmark analysis. With further follow-up the hazard ratio is slightly above 1.0 meaning there was no difference in survival between the doublet and between Sutent. So that certainly bears watching as the data continues to mature. The early argument was that pembrolizumab axitinib was better by overall survival across all risk subsets of renal cell carcinoma and as we continue to follow that statement is no longer accurate for the most recent update. There is still better overall response rate, better progression free survival for the doublet versus Sutent in the good risk patients so there is still clinical rationale to prefer that combination certainly over sunitinib. But that is an area of some uncertainty in the field about the good risk patients, what really is the optimal therapy for those patients.
The second observation from the same dataset, the same update, that I thought was interesting is that again with extended follow-up the complete response rate has increased from the primary publication of 6% now to 9%. That has been one of the features that has been called out as a subtle discriminator between the ipilimumab nivolumab doublet in CheckMate-214 and pembrolizumab axitinib is that there seems to be a perhaps higher complete response rate with the immunotherapy doublet ipilimumab nivolumab. So as the data matures with longer follow-up if pembrolizumab axitinib begins to look very much like the competing frontline doublet that may really not be a discriminator between the two regimens. So I thought those two elements of the updated analysis from KEYNOTE 426 were of interest to the field.
Another interesting abstract and presentation from ASCO 2020 was a summary of the data from the NCI campus testing the doublet bevacizumab plus erlotinib. Bevacizumab an antibody targeting VEGF, erlotinib a tyrosine kinase inhibitor blocking epidermal growth factor receptor signalling, and having provocative activity in two cohorts in that dataset – a cohort of patients that have hereditary renal cell carcinoma defined by a fumarate hydratase mutation. So hereditary leiomyomatosis and renal cell carcinoma and then a second cohort of papillary kidney cancer without a hereditary genetic phenotype. Both cohorts faring well, the hereditary patients, although these are rare patients, fared extremely well in that cohort but the sporadic papillary tumour cells also faring very well. So this provides a novel doublet that currently does not have a formal FDA approval but I anticipate this likely will be incorporated into guideline instruction for providers as a sensible regimen that might be offered to patients with papillary renal cell carcinoma.
So that was nice to see; it has been an ongoing study many of us are familiar with but to see the data summarised at ASCO 2020. It likely will begin to make its way into routine clinical practice for many of us.